Is CPT2 p.Pro227fs (c.674_677dup) pathogenic?

CPT2 p.Pro227fs (c.674677dup) is classified Pathogenic in CPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). Absent from gnomAD; Associated with carnitine palmitoyltransferase II deficiency.

What condition is associated with CPT2 p.Pro227fs (c.674_677dup)?

CPT2 p.Pro227fs (c.674_677dup) is associated with carnitine palmitoyltransferase II deficiency (ClinVar).

How common is CPT2 p.Pro227fs (c.674_677dup) in the general population?

CPT2 p.Pro227fs (c.674_677dup) is absent from gnomAD (gnomAD).

How is Carnitine palmitoyltransferase II deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CPT2 p.Pro227fs

c.674_677dup · rs2525587370 · VCV2720400

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

carnitine palmitoyltransferase II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CPT2
Protein: p.Pro227fs
Coding: c.674_677dup
MANE Select: NM_000098
dbSNP: rs2525587370
Type: Duplication
Location: chr1:53210347 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 227: a UniProt-annotated variant site (in cpt2d)

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

carnitine palmitoyltransferase II deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Carnitine palmitoyltransferase II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

CPT2 p.Pro227Leu Pathogenic/Likely pathogenic ★★ same residue
CPT2 p.Pro227= Likely benign ★ same residue
CPT2 p.Arg303fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Asn349fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Asp279fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Lys537fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Pro211fs Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Thr442fs Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cpt2-p-pro227fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown